Diabetes mellitus and its complications are now considered to be the third leading cause of death in Canada and the United States, trailing only cancer and cardiovascular disease. According to a report issued by the National Commission on Diabetes, as many as 10 million North Americans may have diabetes, and the incidence is increasing yearly. Although the acute and often lethal symptoms of diabetes can be controlled by insulin therapy, the long-term complications reduce life expectancy by as much as one third. Compared with rates of incidence in nondiabetic normal persons, diabetic patients show rates which are increased 25-fold for blindness, 17-fold for kidney disease, 5-fold for gangrene, and 2-fold for heart disease.
There are 2 major forms of diabetes mellitus. One is type I diabetes, which is also known as insulin-dependent diabetes mellitus (IDDM), and the other is type II diabetes, which is also known as noninsulin-dependent diabetes mellitus (NIDDM). Most patients with IDDM have a common pathological picture: the nearly total disappearance of insulin-producing pancreatic beta cells which results in hyperglycemia.sup.1-7.
Considerable evidence has been accumulated showing that most IDDM is the consequence of progressive beta-cell destruction during an asymptomatic period often extending over many years.sup.1-7. The prediabetic period can be recognized by the detection of circulating islet-cell autoantibodies and insulin autoantibodies. The hypothesis that IDDM is an autoimmune disease has been considerably strengthened by studies on the nonobese diabetic (NOD) mouse.sup.8-12 and the BioBreeding (BB) rat.sup.13-27. Both of these animals develop IDDM spontaneously and their diabetic syndromes share many pathological features with that of humans with IDDM.
Diabetes research has been directed toward prevention and cure of IDDM. To date, therapy of IDDM in humans by methods designed to suppress the autoimmune response has proved to be largely unsuccessful. Immunosuppressive therapy utilizing glucocorticoids and cyclophosphamide did not alter the course of the disease. Although studies on the use of cyclosporin A in diabetes appear to be encouraging, generalized immunosuppression involves potential complications including infections and drug-induced kidney and liver damage.
There is a need for a compound which would be nontoxic and have no side effects but which would prevent clinical IDDM completely. A preferred drug would be administered noninvasively, such as an orally administered solution or tablet.